scholarly journals Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study

BMJ ◽  
2019 ◽  
pp. l2327 ◽  
Author(s):  
Rebecca C Richmond ◽  
Emma L Anderson ◽  
Hassan S Dashti ◽  
Samuel E Jones ◽  
Jacqueline M Lane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Protective Effect ◽  
Sleep Duration ◽  
Breast Cancer Diagnosis ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Multivariable Regression ◽  
Insomnia Symptoms

Abstract Objective To examine whether sleep traits have a causal effect on risk of breast cancer. Design Mendelian randomisation study. Setting UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study. Participants 156 848 women in the multivariable regression and one sample mendelian randomisation (MR) analysis in UK Biobank (7784 with a breast cancer diagnosis) and 122 977 breast cancer cases and 105 974 controls from BCAC in the two sample MR analysis. Exposures Self reported chronotype (morning or evening preference), insomnia symptoms, and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits. Main outcome measure Breast cancer diagnosis. Results In multivariable regression analysis using UK Biobank data on breast cancer incidence, morning preference was inversely associated with breast cancer (hazard ratio 0.95, 95% confidence interval 0.93 to 0.98 per category increase), whereas there was little evidence for an association between sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated with sleep duration, and 57 SNPs associated with insomnia symptoms, one sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (0.85, 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two sample MR using data from BCAC supported findings for a protective effect of morning preference (inverse variance weighted odds ratio 0.88, 95% confidence interval 0.82 to 0.93 per category increase) and adverse effect of increased sleep duration (1.19, 1.02 to 1.39 per hour increase) on breast cancer risk (both oestrogen receptor positive and oestrogen receptor negative), whereas evidence for insomnia symptoms was inconsistent. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy. Conclusions Findings showed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.

scholarly journals Investigating causal relationships between sleep traits and risk of breast cancer: a Mendelian randomization study

2018 ◽  
Author(s):  
Rebecca C. Richmond ◽  
Emma L. Anderson ◽  
Hassan S. Dashti ◽  
Samuel E. Jones ◽  
Jacqueline M. Lane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Effect ◽  
Protective Effect ◽  
Sleep Duration ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
Multivariable Regression ◽  
Using Data ◽  
Randomization Analysis ◽  
Insomnia Symptoms

AbstractObjectiveTo examine whether sleep traits have a causal effect on risk of breast cancer.DesignMultivariable regression, one- and two-sample Mendelian randomization.SettingThe UK Biobank prospective cohort study and the Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.Participants156,848 women in the multivariable regression and one-sample Mendelian randomization analysis in UK Biobank (7,784 with a breast cancer diagnosis) and 122,977 breast cancer cases and 105,974 controls from BCAC in the two-sample Mendelian randomization analysis.ExposuresSelf-reported chronotype (morning/evening preference), insomnia symptoms and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.Main outcome measuresBreast cancer (prevalent and incident cases in UK Biobank, prevalent cases only in BCAC).ResultsIn multivariable regression analysis using data on breast cancer incidence in UK Biobank, morning preference was inversely associated with breast cancer (HR 0.95, 95% CI 0.93, 0.98 per category increase) while there was little evidence for an association with sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated sleep duration and 57 SNPs associated with insomnia symptoms, one-sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (HR 0.85, 95% 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two-sample MR using data from BCAC supported findings for a protective effect of morning preference (OR 0.88, 95% CI 0.82, 0.93 per category increase) and adverse effect of increased sleep duration (OR 1.19, 95% CI 1.02, 1.39 per hour increase) on breast cancer (both estrogen receptor positive and negative), while there was inconsistent evidence for insomnia symptoms. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.ConclusionsWe found consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of sleep duration on breast cancer risk.

scholarly journals Thyroid dysfunction and breast cancer risk among women in the UK Biobank cohort

2021 ◽  
Author(s):  
Thi‐Van‐Trinh Tran ◽  
Camille Maringe ◽  
Sara Benitez Majano ◽  
Bernard Rachet ◽  
Marie‐Christine Boutron‐Ruault ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Thyroid Dysfunction ◽  
Uk Biobank ◽  
The Uk

scholarly journals Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

2021 ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Endogenous Hormones ◽  
Uk Biobank ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

scholarly journals Relation of Quantitative Histologic and Radiologic Breast Tissue Composition Metrics with Invasive Breast Cancer Risk

2021 ◽  
Author(s):  
Mustapha Abubakar ◽  
Shaoqi Fan ◽  
Erin Aiello Bowles ◽  
Lea Widemann ◽  
Máire A Duggan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Statistical Tests ◽  
Predictive Biomarkers ◽  
Breast Cancer Diagnosis ◽  
Breast Cancer Risk Factor ◽  
Computer Assisted ◽  
Tissue Composition

Abstract Background Benign breast disease (BBD) is a strong breast cancer risk factor but identifying patients that might develop invasive breast cancer remains a challenge. Methods By applying machine-learning to digitized H&E-stained biopsies and computer-assisted thresholding to mammograms obtained circa BBD diagnosis, we generated quantitative tissue composition metrics and determined their association with future invasive breast cancer diagnosis. Archival breast biopsies and mammograms were obtained for women (18-86 years of age) in a case-control study, nested within a cohort of 15,395 BBD patients from Kaiser Permanente Northwest (1970-2012), followed through mid-2015. Cases (n = 514) who developed incident invasive breast cancer and controls (n = 514) were matched on BBD diagnosis age and plan membership duration. All statistical tests were 2-sided. Results Increasing epithelial area on the BBD biopsy was associated with increasing breast cancer risk (Odds ratio [OR]Q4 vs Q1=1.85, 95% confidence interval [CI] = 1.13-3.04; Ptrend=0.02). Conversely, increasing stroma was associated with decreased risk in non-proliferative, but not proliferative, BBD (Pheterogeneity=0.002). Increasing epithelium-to-stroma proportion [ORQ4 vs Q1=2.06, 95% CI = 1.28-3.33; Ptrend=0.002) and percent mammographic density (MBD) (ORQ4 vs Q1=2.20, 95% CI = 1.20-4.03; Ptrend=0.01) were independently and strongly predictive of increased breast cancer risk. In combination, women with high epithelium-to-stroma proportion/high MBD had substantially higher risk than those with low epithelium-to-stroma proportion/low MBD [OR = 2.27, 95% CI = 1.27-4.06; Ptrend=0.005), particularly among women with non-proliferative (Ptrend=0.01) versus proliferative (Ptrend=0.33) BBD. Conclusion Among BBD patients, increasing epithelium-to-stroma proportion on BBD biopsies and percent MBD at BBD diagnosis were independently and jointly associated with increasing breast cancer risk. These findings were particularly striking for women with non-proliferative disease (comprising approximately 70% of all BBD patients), for whom relevant predictive biomarkers are lacking.

scholarly journals Sleep duration and breast cancer incidence: results from the Million Women Study and meta-analysis of published prospective studies

SLEEP ◽  
2020 ◽  
Author(s):  
Angel T Y Wong ◽  
Alicia K Heath ◽  
Tammy Y N Tong ◽  
Gillian K Reeves ◽  
Sarah Floud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Sleep Duration ◽  
Cancer Incidence ◽  
Prospective Studies ◽  
Average Duration ◽  
Meta Analysis ◽  
Breast Cancer Incidence ◽  
Weighted Average

Abstract Study Objectives To investigate the association between sleep duration and breast cancer incidence, we examined the association in a large UK prospective study and conducted a meta-analysis of prospective studies. Methods In the Million Women Study, usual sleep duration over a 24-h period was collected in 2001 for 713,150 participants without prior cancer, heart problems, stroke, or diabetes (mean age = 60 years). Follow-up for breast cancer was by record linkage to national cancer registry data for 14.3 years on average from the 3-year resurvey. Cox regression models yielded multivariable-adjusted breast cancer relative risks (RR) and 95% confidence intervals (CIs) for sleep duration categories. Published prospective studies of sleep duration and breast cancer risk were included in a meta-analysis, which estimated the inverse-variance weighted average of study-specific log RRs for short and for long versus average duration sleep. Results After excluding the first 5 years to minimize reverse causation bias in the Million Women Study, 24,476 women developed breast cancer. Compared with 7–8 h of sleep, the RRs for <6, 6, 9, and >9 h of sleep were 1.01 (95% CI, 0.95–1.07), 0.99 (0.96–1.03), 1.01 (0.96–1.06), and 1.03 (0.95–1.12), respectively. In a meta-analysis of 14 prospective studies plus the Million Women Study, including 65,410 breast cancer cases, neither short (RR < 7 h = 0.99 [0.98–1.01]) nor long (RR > 8 h = 1.01 [0.98–1.04]) versus average duration sleep was associated with breast cancer risk. Conclusions The totality of the prospective evidence does not support an association between sleep duration and breast cancer risk.

scholarly journals Association of Nongenetic Factors With Breast Cancer Risk in Genetically Predisposed Groups of Women in the UK Biobank Cohort

2020 ◽  
Vol 3 (4) ◽  
pp. e203760
Author(s):  
Kawthar Al Ajmi ◽  
Artitaya Lophatananon ◽  
Krisztina Mekli ◽  
William Ollier ◽  
Kenneth R. Muir
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Uk Biobank ◽  
The Uk

scholarly journals Physical activity and breast cancer risk: results from the UK Biobank prospective cohort

2020 ◽  
Vol 122 (5) ◽  
pp. 726-732 ◽  
Author(s):  
Wenji Guo ◽  
Georgina K. Fensom ◽  
Gillian K. Reeves ◽  
Timothy J. Key
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cox Regression ◽  
Postmenopausal Breast Cancer ◽  
Protective Role ◽  
Accelerometer Data ◽  
Uk Biobank ◽  
Relative Risks

Abstract Background Previous studies suggest a protective role of physical activity in breast cancer risk, largely based on self-reported activity. We aimed to clarify this association by examining breast cancer risk in relation to self-reported physical activity, informed by accelerometer-based measures in a large subset of participants. Methods We analysed data from 47,456 premenopausal and 126,704 postmenopausal women in UK Biobank followed from 2006 to 2014. Physical activity was self-reported at baseline, and at resurvey in a subsample of 6443 participants. Accelerometer data, measured from 2013 to 2015, were available in 20,785 women. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using multivariable-adjusted Cox regression. Results A total of 3189 cases were diagnosed during follow-up (mean = 5.7 years). Women in the top compared with the bottom quartile of self-reported physical activity had a reduced risk of both premenopausal (RR 0.75; 95% CI 0.60–0.93) and postmenopausal breast cancer (RR 0.87; 95% CI 0.78–0.98), after adjusting for adiposity. In analyses utilising physical activity values assigned from accelerometer measurements, an increase of 5 milli-gravity was associated with a 21% (RR 0.79; 95% CI 0.66–0.95) reduction in premenopausal and a 16% (RR 0.84; 95% CI 0.73–0.96) reduction in postmenopausal breast cancer risk. Conclusions Greater physical activity is associated with a reduction in breast cancer risk, which appears to be independent of any association it may have on risk through its effects on adiposity.

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